Masanari Inoue

Three-dimensional evaluation of healing joint morphology after closed treatment of condylar fractures

Closed treatment for condylar fractures has long been widely accepted. With closed treatment, the deviated bone fragments heal in their new positions, and this may subsequently cause a range of functional impairments. The association between healing morphology and post-treatment functional impairment is unclear. In this study, computed tomography images of 26 patients (35 sides) who had undergone closed treatment for condylar fractures were used to perform a comparative investigation of three-dimensional (3D) bone morphology before and after treatment. As a result, the morphology of the condylar process after treatment was classified into four different patterns: unchanged, spherical, L-shaped, and detached. In terms of the association between fracture types and healing morphology, fractures of the condylar head healed in the spherical pattern, simple fractures of the condylar neck healed in the spherical or L-shaped pattern, and comminuted fractures of the condylar neck healed in the spherical, L-shaped, or detached pattern. The association between mandibular deviation and healing morphology was also investigated, and it was found that deviation was greater for the spherical and detached patterns than for the L-shaped pattern. The present findings indicate that 3D evaluation of the fractured condylar process is required to elucidate the association with functional impairment after healing.

Oxytocin produces a membrane depolarization in adult rat spinal substantia gelatinosa neurons

The development of pain after peripheral nerve and tissue injury involves not only neuronal pathways but also glia. However, uncertainty still remains as to the relative contribution of different types of glial cells in the development of the pain-related enhanced response states. We examined the contribution of glial cells to the central sensitization in the rat spinal dorsal horn which is induced in neuropathic pain and inflammatory pain. In rats subjected to neuropathic pain, the immunoreactivity (IR) of microglial marker OX 42 was largely increased. In rats subjected to inflammatory pain, IR of astosytes marker GFAP was slightly increased. The optically-recorded neuronal excitation induced by single-pulse stimulation to the dorsal root was augmented in rats subjected to neuropathic pain and rats subjected to inflammatory pain by comparison to control rats. The bath application of a microglial inhibitor minocycline and a p38 mitogen-activated protein kinase inhibitor SB203580 inhibited the neuronal excitation in rats subjected to neuropathic pain, but not in control and rats subjected to inflammatory pain. PPADS slightly inhibited the neuronal excitation in all group. The additional perfusion of TNP-ATP in PPADS largely inhibited the neuronal excitation in rats subjected to neuropathic pain. In contrast, an astroglial toxin L-alpha-aminoadipate and a gap junction blocker carbenoxolone inhibited the neuronal excitation in rats subjected to inflammatory pain, but not in control and rats subjected to neuropathic pain. The larger number of cells in the spinal cord slice taken from rats subjected to neuropathic pain showed the Ca2+ signal by puff application of ATP to comparison with control and rats subjected to inflammatory pain. The Ca2+ signal was inhibited by minocycline and TNP-ATP. Research fund: KAKENHI22600005.

Opioids reduce the peak amplitude of action potential in adult rat dorsal root ganglion neurons

GABA and glycine are important inhibitory neurotransmitters in the central nervous system and are loaded into synaptic vesicles via the vesicular GABA transporter (VGAT). Due to the evidence linking alterations in GABAergic and/or glycinergic neurotransmission to various pain disorders, we investigated the possible influence of downregulation of VGAT on pain threshold in mice. The phenotypes of heterozygous VGAT knockout (VGAT+/−) mice were compared to wild-type (WT) mice using behavioral and electrophysiological assays. Western blot analysis showed significant reduction of VGAT protein levels in VGAT+/− mice brain (47.8% of WT mice) and spinal cord (61.0% of WT mice). However, HPLC revealed that glutamate, GABA, and glycine contents in the whole brain and spinal cord were no changed in VGAT+/− mice. Although behavioral analysis of VGAT+/− mice showed unchanged motor coordination, anxiety, memory performance and anesthetic sensitivity to propofol and ketamine, thermal nociception and inflammatory pain were enhanced. Patch-clamp recordings revealed that the frequency and amplitude of glycinergic mIPSCs in dorsal horn neurons were reduced in VGAT+/− mice. Genotype differences in glycinergic mIPSCs were more evident during sustained stimulation by high potassium solutions. It seemed that the estimated size of the readily releasable pool (RRP) of glycine-containing vesicles was reduced in VGAT+/− mice. Taken together, our results provide genetic, behavioral and electrophysiological evidence that reduction of VGAT-mediated inhibitory drive in the spinal cord alters very specific forms of pain processing. Research fund: KAKENHI (40447264).